CN1293665A - 新化合物及其用作阳性ampa受体调节剂 - Google Patents
新化合物及其用作阳性ampa受体调节剂 Download PDFInfo
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- CN1293665A CN1293665A CN99804196A CN99804196A CN1293665A CN 1293665 A CN1293665 A CN 1293665A CN 99804196 A CN99804196 A CN 99804196A CN 99804196 A CN99804196 A CN 99804196A CN 1293665 A CN1293665 A CN 1293665A
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- alkyl
- aryl
- arbitrarily
- dioxide
- tetrahydro
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 319
- 102000003678 AMPA Receptors Human genes 0.000 title claims abstract description 26
- 108090000078 AMPA Receptors Proteins 0.000 title claims abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 239
- 239000001257 hydrogen Substances 0.000 claims abstract description 238
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 105
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 372
- 238000000034 method Methods 0.000 claims description 273
- 125000003545 alkoxy group Chemical group 0.000 claims description 232
- -1 amino, sulfenyl Chemical group 0.000 claims description 231
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 209
- 125000003118 aryl group Chemical group 0.000 claims description 207
- 229910052736 halogen Inorganic materials 0.000 claims description 190
- 150000002367 halogens Chemical class 0.000 claims description 190
- 125000000623 heterocyclic group Chemical group 0.000 claims description 185
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 162
- 150000002431 hydrogen Chemical class 0.000 claims description 133
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 119
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 101
- 125000000304 alkynyl group Chemical group 0.000 claims description 99
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 99
- 125000001188 haloalkyl group Chemical group 0.000 claims description 91
- 239000000460 chlorine Substances 0.000 claims description 87
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 68
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 62
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 56
- 150000001412 amines Chemical class 0.000 claims description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 45
- 201000010099 disease Diseases 0.000 claims description 40
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 40
- 229910052801 chlorine Inorganic materials 0.000 claims description 39
- 229910052794 bromium Inorganic materials 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 230000015572 biosynthetic process Effects 0.000 claims description 33
- 125000004429 atom Chemical group 0.000 claims description 32
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 30
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 30
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 29
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 29
- 125000005842 heteroatom Chemical group 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 28
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- 150000003053 piperidines Chemical group 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 20
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 18
- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 17
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 16
- 238000006467 substitution reaction Methods 0.000 claims description 16
- 125000002837 carbocyclic group Chemical group 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 13
- 208000024827 Alzheimer disease Diseases 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 13
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 229940124530 sulfonamide Drugs 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 125000005574 norbornylene group Chemical group 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 7
- 230000035945 sensitivity Effects 0.000 claims description 7
- 210000003169 central nervous system Anatomy 0.000 claims description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 230000002950 deficient Effects 0.000 claims description 6
- 150000002829 nitrogen Chemical class 0.000 claims description 6
- 208000012201 sexual and gender identity disease Diseases 0.000 claims description 6
- 208000015891 sexual disease Diseases 0.000 claims description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 5
- 206010039966 Senile dementia Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 208000024732 dysthymic disease Diseases 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 5
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 4
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 claims description 4
- PMZBHPUNQNKBOA-UHFFFAOYSA-N 5-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=CC(C(O)=O)=CC(C(O)=O)=C1 PMZBHPUNQNKBOA-UHFFFAOYSA-N 0.000 claims description 4
- 208000007848 Alcoholism Diseases 0.000 claims description 4
- 208000000044 Amnesia Diseases 0.000 claims description 4
- 206010003805 Autism Diseases 0.000 claims description 4
- 208000020706 Autistic disease Diseases 0.000 claims description 4
- 201000006474 Brain Ischemia Diseases 0.000 claims description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 4
- 206010013654 Drug abuse Diseases 0.000 claims description 4
- 208000026139 Memory disease Diseases 0.000 claims description 4
- 208000028017 Psychotic disease Diseases 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 201000007930 alcohol dependence Diseases 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 206010008118 cerebral infarction Diseases 0.000 claims description 4
- 230000006735 deficit Effects 0.000 claims description 4
- ZICQBHNGXDOVJF-UHFFFAOYSA-N diamantane Chemical compound C1C2C3CC(C4)CC2C2C4C3CC1C2 ZICQBHNGXDOVJF-UHFFFAOYSA-N 0.000 claims description 4
- 206010015037 epilepsy Diseases 0.000 claims description 4
- 230000006984 memory degeneration Effects 0.000 claims description 4
- 208000023060 memory loss Diseases 0.000 claims description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
- XIUYBDCCFRIFSK-UHFFFAOYSA-N n,n,3-trimethyl-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1=C(C)NS(=O)(=O)C2=CC(S(=O)(=O)N(C)C)=CC=C21 XIUYBDCCFRIFSK-UHFFFAOYSA-N 0.000 claims description 4
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 claims description 4
- 208000011117 substance-related disease Diseases 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- PDXCOWCINSIDPO-UHFFFAOYSA-N 2h-thiadiazine 1,1-dioxide Chemical compound O=S1(=O)NN=CC=C1 PDXCOWCINSIDPO-UHFFFAOYSA-N 0.000 claims description 3
- 206010052428 Wound Diseases 0.000 claims description 3
- 208000027418 Wounds and injury Diseases 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000001537 neural effect Effects 0.000 claims description 3
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 claims description 3
- QDOQLKXQYLZYEA-UHFFFAOYSA-N (3-cyclohexyl-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazin-8-yl)methanol Chemical compound N1S(=O)(=O)C=2C(CO)=CC=CC=2NC1C1CCCCC1 QDOQLKXQYLZYEA-UHFFFAOYSA-N 0.000 claims description 2
- LCDBKCCPUXCASM-UHFFFAOYSA-N 1,1-dioxo-3-phenyl-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1S(=O)(=O)C2=CC(S(=O)(=O)N)=CC=C2N=C1C1=CC=CC=C1 LCDBKCCPUXCASM-UHFFFAOYSA-N 0.000 claims description 2
- ZPASABDAIAXPEY-UHFFFAOYSA-N 1-sulfonyl-2,3-dihydropyrrolo[2,1-c][1,2,4]benzothiadiazine 5,5-dioxide Chemical compound S(=O)(=O)=C1CCC2=NS(C3=C(N21)C=CC=C3)(=O)=O ZPASABDAIAXPEY-UHFFFAOYSA-N 0.000 claims description 2
- RWUDZOCZVQBJNI-UHFFFAOYSA-N 2,3,10,10a-tetrahydro-1h-pyrrolo[1,2-b][1,2,4]benzothiadiazine 5,5-dioxide Chemical compound N1C2=CC=CC=C2S(=O)(=O)N2C1CCC2 RWUDZOCZVQBJNI-UHFFFAOYSA-N 0.000 claims description 2
- BQFHXNJPWFQYES-UHFFFAOYSA-N 2-(3-cyclohexyl-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazin-7-yl)-n,n-dimethylbenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=CC=C1C1=CC=C(NC(NS2(=O)=O)C3CCCCC3)C2=C1 BQFHXNJPWFQYES-UHFFFAOYSA-N 0.000 claims description 2
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 2
- JURGPCFAAKMAIA-UHFFFAOYSA-N 2-cyclohexyl-1,2,3,4-tetrahydroquinazoline-6-sulfonamide Chemical compound N1CC2=CC(S(=O)(=O)N)=CC=C2NC1C1CCCCC1 JURGPCFAAKMAIA-UHFFFAOYSA-N 0.000 claims description 2
- CCCLGUCOGQADHQ-UHFFFAOYSA-N 2-ethyl-2-methyl-3h-1,3-benzoxazin-4-one Chemical compound C1=CC=C2OC(CC)(C)NC(=O)C2=C1 CCCLGUCOGQADHQ-UHFFFAOYSA-N 0.000 claims description 2
- MOFJSTXFUSYCDO-UHFFFAOYSA-N 2-methyl-2,3-dihydro-1,3-benzoxazin-4-one Chemical compound C1=CC=C2OC(C)NC(=O)C2=C1 MOFJSTXFUSYCDO-UHFFFAOYSA-N 0.000 claims description 2
- AMZRLVJMBHMIPA-UHFFFAOYSA-N 2-phenyl-2,3-dihydro-1,3-benzoxazin-4-one Chemical compound O1C2=CC=CC=C2C(=O)NC1C1=CC=CC=C1 AMZRLVJMBHMIPA-UHFFFAOYSA-N 0.000 claims description 2
- ZXTHWIZHGLNEPG-UHFFFAOYSA-N 2-phenyl-4,5-dihydro-1,3-oxazole Chemical compound O1CCN=C1C1=CC=CC=C1 ZXTHWIZHGLNEPG-UHFFFAOYSA-N 0.000 claims description 2
- UOCUSOBVEHOMMB-UHFFFAOYSA-N 2h-1$l^{6},2,3-benzothiadiazine 1,1-dioxide Chemical compound C1=CC=C2S(=O)(=O)NN=CC2=C1 UOCUSOBVEHOMMB-UHFFFAOYSA-N 0.000 claims description 2
- XSVCDKNLLZPUHQ-UHFFFAOYSA-N 3-(1-adamantyl)-5,7-dibromo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1C(C2)CC(C3)CC2CC13C1NC2=C(Br)C=C(Br)C=C2S(=O)(=O)N1 XSVCDKNLLZPUHQ-UHFFFAOYSA-N 0.000 claims description 2
- IXKMHMLMLKFTME-UHFFFAOYSA-N 3-cyclohexyl-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazin-7-amine Chemical compound N1S(=O)(=O)C2=CC(N)=CC=C2NC1C1CCCCC1 IXKMHMLMLKFTME-UHFFFAOYSA-N 0.000 claims description 2
- XUQWBBUOVQYUAZ-UHFFFAOYSA-N 3-cyclohexyl-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-carbonitrile Chemical compound N1C2=CC=C(C#N)C=C2S(=O)(=O)NC1C1CCCCC1 XUQWBBUOVQYUAZ-UHFFFAOYSA-N 0.000 claims description 2
- IWCUSNNKTQYZRR-UHFFFAOYSA-N 3-cyclohexyl-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-carboxamide Chemical compound N1S(=O)(=O)C2=CC(C(=O)N)=CC=C2NC1C1CCCCC1 IWCUSNNKTQYZRR-UHFFFAOYSA-N 0.000 claims description 2
- RGDFUTUYFYKNHL-UHFFFAOYSA-N 3-cyclohexyl-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1S(=O)(=O)C2=CC(S(=O)(=O)N)=CC=C2NC1C1CCCCC1 RGDFUTUYFYKNHL-UHFFFAOYSA-N 0.000 claims description 2
- RKQNBZGBUDFCGQ-UHFFFAOYSA-N 3-cyclohexyl-6-(2-methoxyphenyl)-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound COC1=CC=CC=C1C1=CC=C2S(=O)(=O)NC(C3CCCCC3)NC2=C1 RKQNBZGBUDFCGQ-UHFFFAOYSA-N 0.000 claims description 2
- ISRRWUNTXIBXAA-UHFFFAOYSA-N 3-cyclohexyl-6-(2-methoxyphenyl)-7-methyl-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound COC1=CC=CC=C1C(C(=C1)C)=CC2=C1S(=O)(=O)NC(C1CCCCC1)N2 ISRRWUNTXIBXAA-UHFFFAOYSA-N 0.000 claims description 2
- YHCXRGBPUHDXAT-UHFFFAOYSA-N 3-cyclohexyl-6-methyl-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1S(=O)(=O)C=2C=C(S(N)(=O)=O)C(C)=CC=2NC1C1CCCCC1 YHCXRGBPUHDXAT-UHFFFAOYSA-N 0.000 claims description 2
- LTTNPGLVTMWWQN-UHFFFAOYSA-N 3-cyclohexyl-7-(1-methylimidazol-2-yl)-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound CN1C=CN=C1C1=CC=C(NC(NS2(=O)=O)C3CCCCC3)C2=C1 LTTNPGLVTMWWQN-UHFFFAOYSA-N 0.000 claims description 2
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- ZJYBPAKREINUPO-UHFFFAOYSA-N 3-cyclohexyl-7-(2-methoxyphenyl)-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound COC1=CC=CC=C1C1=CC=C(NC(NS2(=O)=O)C3CCCCC3)C2=C1 ZJYBPAKREINUPO-UHFFFAOYSA-N 0.000 claims description 2
- JOOYBBYBBFKNIT-UHFFFAOYSA-N 3-cyclohexyl-7-(4-methylpiperidin-1-yl)sulfonyl-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine 1,1-dioxide Chemical compound CC1CCN(CC1)S(=O)(=O)C2=CC3=C(C=C2)NC(NS3(=O)=O)C4CCCCC4 JOOYBBYBBFKNIT-UHFFFAOYSA-N 0.000 claims description 2
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- SJXMJUXZVDLBTM-UHFFFAOYSA-N 3-cyclohexyl-8-methyl-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound N1S(=O)(=O)C=2C(C)=CC=CC=2NC1C1CCCCC1 SJXMJUXZVDLBTM-UHFFFAOYSA-N 0.000 claims description 2
- OFRSZWPEVPVADE-UHFFFAOYSA-N 3-cyclohexyl-n,n-diethyl-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1S(=O)(=O)C2=CC(S(=O)(=O)N(CC)CC)=CC=C2NC1C1CCCCC1 OFRSZWPEVPVADE-UHFFFAOYSA-N 0.000 claims description 2
- PMMNAVXGIVYGHU-UHFFFAOYSA-N 3-phenyl-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound N1C2=CC=CC=C2S(=O)(=O)NC1C1=CC=CC=C1 PMMNAVXGIVYGHU-UHFFFAOYSA-N 0.000 claims description 2
- YYPWDMFWDGAUPK-UHFFFAOYSA-N 4-oxo-2-(trifluoromethyl)-1h-quinazoline-6-sulfonamide Chemical compound N1=C(C(F)(F)F)NC(=O)C2=CC(S(=O)(=O)N)=CC=C21 YYPWDMFWDGAUPK-UHFFFAOYSA-N 0.000 claims description 2
- CFCVLMZNGXXJGA-UHFFFAOYSA-N 5,7-dibromo-3-methyl-4h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical class C1=C(Br)C=C2S(=O)(=O)NC(C)=NC2=C1Br CFCVLMZNGXXJGA-UHFFFAOYSA-N 0.000 claims description 2
- XGOZNHPMPZJDPE-UHFFFAOYSA-N 5,7-dibromo-3-phenyl-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound N1S(=O)(=O)C2=CC(Br)=CC(Br)=C2NC1C1=CC=CC=C1 XGOZNHPMPZJDPE-UHFFFAOYSA-N 0.000 claims description 2
- PBSYDJWXTZFDNB-UHFFFAOYSA-N 5,7-dibromo-4h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound N1=CNS(=O)(=O)C2=CC(Br)=CC(Br)=C21 PBSYDJWXTZFDNB-UHFFFAOYSA-N 0.000 claims description 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/15—Six-membered rings
- C07D285/16—Thiadiazines; Hydrogenated thiadiazines
- C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
- C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
- C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/15—Six-membered rings
- C07D285/16—Thiadiazines; Hydrogenated thiadiazines
- C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
- C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
- C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
- C07D285/26—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals
- C07D285/28—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| DK22698 | 1998-02-18 | ||
| DK0226/98 | 1998-02-18 |
Publications (1)
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| CN1293665A true CN1293665A (zh) | 2001-05-02 |
Family
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Family Applications (1)
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| CN99804196A Pending CN1293665A (zh) | 1998-02-18 | 1999-02-18 | 新化合物及其用作阳性ampa受体调节剂 |
Country Status (17)
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| EP (1) | EP1071426A2 (xx) |
| JP (1) | JP2002504481A (xx) |
| CN (1) | CN1293665A (xx) |
| AU (1) | AU751384B2 (xx) |
| CA (1) | CA2320354A1 (xx) |
| EE (1) | EE200000468A (xx) |
| HU (1) | HUP0101280A3 (xx) |
| IL (1) | IL137720A0 (xx) |
| IS (1) | IS5581A (xx) |
| NO (1) | NO20004121L (xx) |
| NZ (1) | NZ506251A (xx) |
| PL (1) | PL342843A1 (xx) |
| RU (1) | RU2214405C2 (xx) |
| SK (1) | SK11892000A3 (xx) |
| TR (1) | TR200002427T2 (xx) |
| WO (1) | WO1999042456A2 (xx) |
| ZA (1) | ZA991301B (xx) |
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| CN1308317C (zh) * | 2004-01-26 | 2007-04-04 | 瑟维尔实验室 | 新的氟化苯并噻二嗪化合物，它们的制备方法和含有它们的药物组合物 |
| CN102361860A (zh) * | 2009-03-20 | 2012-02-22 | 瑟维尔实验室 | 用作ampa和nmda受体调节剂的苯并硫杂二氮杂*衍生物 |
| CN102958919A (zh) * | 2010-07-02 | 2013-03-06 | 霍夫曼-拉罗奇有限公司 | 新的四氢喹啉衍生物 |
| CN102977054A (zh) * | 2012-12-12 | 2013-03-20 | 中国药科大学 | 一类选择性α2A受体激动剂的治疗阿尔茨海默病用途 |
| CN103153973A (zh) * | 2010-09-16 | 2013-06-12 | 瑟维尔实验室 | 二氢苯并氧硫氮杂*衍生物、其制备方法、包含此类化合物的药用组合物以及它们作为ampa受体调节剂的用途 |
| CN103319381A (zh) * | 2013-06-14 | 2013-09-25 | 湖州康企药业有限公司 | 一种高纯度精磺胺的制备方法 |
| CN105294599A (zh) * | 2015-09-17 | 2016-02-03 | 三峡大学 | 一种噻二嗪类化合物及其不对称的合成方法 |
| CN106946920A (zh) * | 2017-04-05 | 2017-07-14 | 泰力特医药（湖北）有限公司 | 一种4‑氨基苯硼酸衍生物的制备方法 |
| CN111018750A (zh) * | 2019-12-19 | 2020-04-17 | 苏州诚和医药化学有限公司 | 一种2,3-二甲氧基-5-磺酰胺基苯甲酸的制备新方法 |
| CN111100042A (zh) * | 2019-11-18 | 2020-05-05 | 苏州诚和医药化学有限公司 | 一种2-甲氧基-5-磺酰胺基苯甲酸的制备方法 |
| WO2020253860A1 (zh) * | 2019-06-21 | 2020-12-24 | 江苏豪森药业集团有限公司 | 芳基磷氧化物类衍生物抑制剂、其制备方法和应用 |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7671200B2 (en) | 1999-10-27 | 2010-03-02 | Cytokinetics, Inc. | Quinazolinone KSP inhibitors |
| DE10004572A1 (de) * | 2000-02-02 | 2001-08-09 | Boehringer Ingelheim Pharma | Neue positive allosterische AMPA-Rezeptor Modulatoren (PAARM), Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| FR2812291B1 (fr) * | 2000-07-28 | 2002-12-13 | Adir | Nouveaux derives de benzothiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CN1314351A (zh) * | 2001-03-22 | 2001-09-26 | 刘志红 | 喹唑啉酮合成方法及具有抗癌作用的一类喹唑啉酮化合物 |
| TWI232863B (en) * | 2001-06-11 | 2005-05-21 | Akzo Nobel Nv | Benzoxazepine derivatives |
| WO2002102808A2 (en) | 2001-06-14 | 2002-12-27 | Akzo Nobel N.V. | (PYRIDO/THIENO)-[f]-OXAZEPIN-5-ONE DERIVATIVES AS POSITIVE MODULATORS OF THE AMPA RECEPTOR |
| CA2458388A1 (en) * | 2001-10-10 | 2003-04-17 | Neurosearch A/S | Novel benzothiazine derivatives, their preparation and use |
| MXPA04004815A (es) * | 2001-11-26 | 2005-02-17 | Cortex Pharma Inc | Compuestos de carbonilbenzoxazina para mejorar respuestas sinapticas, glutamatergicas. |
| FR2833956B1 (fr) * | 2001-12-21 | 2004-01-30 | Servier Lab | Nouveaux derives de benzothiazine et de benzothiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2833950B1 (fr) * | 2001-12-21 | 2005-12-16 | Servier Lab | Nouveaux derives de benzothiazine et de benzothiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2833955B1 (fr) | 2001-12-21 | 2004-01-30 | Servier Lab | Nouveaux derives de benzothiazine et de benzothiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2854634B1 (fr) * | 2003-05-05 | 2005-07-08 | Servier Lab | Nouveaux derives de thiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2856064B1 (fr) * | 2003-06-13 | 2005-08-19 | Servier Lab | Nouveaux derives de benzothiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| FR2856065B1 (fr) * | 2003-06-13 | 2005-08-19 | Servier Lab | Nouveaux derives de benzothiazine et benzothiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| JP2009513502A (ja) | 2003-07-02 | 2009-04-02 | エフ．ホフマン−ラ ロシュ アーゲー | アリールアミン置換キナゾリノン化合物 |
| AU2004270162B2 (en) | 2003-08-28 | 2010-05-13 | Nicox S.A. | Nitrosated ad nitrosylated diuretic compouds, compositions and methods of use |
| US7244843B2 (en) | 2003-10-07 | 2007-07-17 | Bristol-Myers Squibb Company | Modulators of serotonin receptors |
| FR2877338B1 (fr) | 2004-11-03 | 2007-01-26 | Servier Lab | Nouveaux derives de benzothiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2877342B1 (fr) | 2004-11-03 | 2007-01-26 | Servier Lab | Nouveaux derives de benzothiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2879201B1 (fr) | 2004-12-10 | 2007-02-16 | Servier Lab | Nouveaux derives de benzothiazine et benzothiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| WO2006086464A2 (en) | 2005-02-10 | 2006-08-17 | Bristol-Myers Squibb Company | Dihydroquinazolinones as 5ht modulators |
| CA2597460A1 (en) | 2005-02-24 | 2006-08-31 | Nitromed, Inc. | Nitric oxide enhancing diuretic compounds, compositions and methods of use |
| GB0507298D0 (en) * | 2005-04-11 | 2005-05-18 | Novartis Ag | Organic compounds |
| TW200800959A (en) | 2005-06-10 | 2008-01-01 | Wyeth Corp | Piperazine-piperidine antagonists and agonists of the 5-HT1a receptor |
| MX2009007242A (es) | 2007-01-03 | 2009-09-02 | Cortex Pharma Inc | Compuesto de [1,2,3]-benzotriazinona 3-sustituida para mejorar respuestas sinapticas glutamatergicas. |
| TW200901974A (en) | 2007-01-16 | 2009-01-16 | Wyeth Corp | Compounds, compositions, and methods of making and using them |
| NZ582035A (en) | 2007-05-17 | 2012-03-30 | Cortex Pharma Inc | Di-substituted amides for enhancing glutamatergic synaptic responses |
| AU2008287445A1 (en) | 2007-08-10 | 2009-02-19 | Cortex Pharmaceuticals, Inc. | Bicyclic amides for enhancing glutamatergic synaptic responses |
| US8119632B2 (en) | 2007-08-10 | 2012-02-21 | Cortex Pharmaceuticals, Inc. | Bicyclic amide derivatives for enhancing glutamatergic synaptic responses |
| FR2933698A1 (fr) | 2008-07-09 | 2010-01-15 | Servier Lab | Nouveaux derives de benzothiadiazines cycloalkylees, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| US8952034B2 (en) | 2009-07-27 | 2015-02-10 | Gilead Sciences, Inc. | Fused heterocyclic compounds as ion channel modulators |
| FR2955107B1 (fr) * | 2010-01-08 | 2012-03-02 | Servier Lab | Nouveaux derives thiochromanes, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2955106B1 (fr) | 2010-01-08 | 2011-12-23 | Servier Lab | Nouveaux derives de benzothiadiazines cyclopropylees, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| AU2011272787B2 (en) | 2010-07-02 | 2015-06-18 | Gilead Sciences, Inc. | Fused heterocyclic compounds as ion channel modulators |
| IT1402905B1 (it) * | 2010-11-29 | 2013-09-27 | Univ Degli Studi Modena E Reggio Emilia | Derivati di 1,2,4-benzotiadiazin 1,1-diossido, loro preparazione e loro impiego come modulatori allosterici del recettore ampa. |
| NZ716420A (en) | 2011-05-10 | 2017-05-26 | Gilead Sciences Inc | Fused heterocyclic compounds as sodium channel modulators |
| NO3175985T3 (xx) | 2011-07-01 | 2018-04-28 | ||
| TW201837023A (zh) | 2011-07-01 | 2018-10-16 | 美商基利科學股份有限公司 | 作為離子通道調節劑之稠合雜環化合物 |
| JO3316B1 (ar) | 2013-05-30 | 2019-03-13 | Lilly Co Eli | مركبات 3، 4-داي هيدرو أيزو كوينولين -2(1h)-يل |
| CN105263924B (zh) | 2013-05-30 | 2018-10-19 | 爱杜西亚制药有限公司 | Cxcr7受体调节剂 |
| CN103275016B (zh) * | 2013-06-04 | 2015-03-11 | 温州医科大学附属第二医院 | 一种2-取代喹唑啉化合物的合成方法 |
| CA2915405A1 (en) | 2013-06-13 | 2014-12-18 | Veroscience Llc | Compositions and methods for treating metabolic disorders |
| CN103772296B (zh) * | 2013-12-19 | 2015-06-17 | 安徽师范大学 | 一种喹唑啉衍生物的合成方法 |
| US10202368B2 (en) | 2014-12-01 | 2019-02-12 | Idorsia Pharmaceuticals Ltd. | CXCR7 receptor modulators |
| RU2726456C1 (ru) * | 2019-10-02 | 2020-07-14 | Общество с ограниченной ответственностью "Научно-исследовательский институт ХимРар" (ООО "НИИ ХимРар") | Ингибитор вируса гепатита В (ВГВ) |
| WO2024115797A2 (en) * | 2022-12-30 | 2024-06-06 | Aexon Labs. Inc. | Dihydro-quinazoline, -benzothiazine and -benzoxazine derivatives and use thereof as orexin receptors agonists for treating or preventing neurological diseases |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3275625A (en) * | 1966-09-27 | Derivatives of | ||
| NL296964A (xx) * | ||||
| FR1217929A (fr) * | 1958-03-03 | 1960-05-06 | Ciba Geigy | Procédé de préparation du 1,1-dioxyde de la 6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine et de ses sels |
| GB863474A (en) * | 1958-08-13 | 1961-03-22 | Knud Abildgaard | Benzothiadiazine derivatives and their preparation |
| DE1125938B (de) * | 1960-02-12 | 1962-03-22 | Thomae Gmbh Dr K | Verfahren zur Herstellung von 7-Sulfamyl-3, 4-dihydro-1, 2, 4-benzothiadiazin-1, 1-dioxyden |
| GB946864A (en) * | 1960-05-06 | 1964-01-15 | Knud Abildgaard | Method for the production of 3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides |
| US3419552A (en) * | 1961-04-12 | 1968-12-31 | Lilly Co Eli | Preparation of substituted dihydrobenzothiadiazine-1,1-dioxides |
| CH475269A (de) * | 1962-04-19 | 1969-07-15 | Hans Voigt Chem Pharm Fabrik D | Verfahren zur Herstellung von 7-Sulfonamido-3,4-dihydro-1,2,4-benzothiadiazin-1,1-dioxyden |
| US3351595A (en) * | 1962-12-07 | 1967-11-07 | Ciba Geigy Corp | Derivatives of 3, 4-dihydro-2h-1, 2, 4-benzothiadiazine-1, 1-dioxide |
| US3311620A (en) * | 1963-05-31 | 1967-03-28 | Stanley C Bell | Fused ring benzothiadiazines |
| US3277086A (en) * | 1964-07-07 | 1966-10-04 | American Home Prod | 1, 2, 4-benzothiadiazine 1, 1-dioxides having a heterocyclic ring fused to the "b" face thereof |
| US4184039A (en) * | 1977-12-01 | 1980-01-15 | Paul Finkelstein | Benzothiadiazine 1, 1-dioxides |
| JPH07505411A (ja) * | 1992-04-15 | 1995-06-15 | ローン−プーラン・ロレ・ソシエテ・アノニム | ３，４−ジヒドロ−１ｈ−１，２，４−ベンゾチアジアジン−１，１−ジオキシド−２−カルボン酸誘導体，それらの製造およびそれらを含有する医学的生成物 |
| US5488049A (en) * | 1993-12-10 | 1996-01-30 | Fidia - Georgetown Institute For The Neuro-Sciences | Method of treating learning and memory disorders using benzothiadiazide derivatives as nootropic agents |
| FR2722502B1 (fr) * | 1994-07-12 | 1996-08-23 | Adir | Nouveau derive de benzothiadiazine, son procede depreparation et les compositions pharmaceutiques qui le contiennent |
| CA2242879C (en) * | 1996-01-29 | 2009-05-26 | The Regents Of The University Of California | Method for treating sexual dysfunctions |
| WO1998012185A1 (en) * | 1996-09-17 | 1998-03-26 | The Regents Of The University Of California | Benzothiadiazide derivatives and their use as allosteric up-modulators of the ampa receptor |
-
1999
- 1999-02-18 PL PL99342843A patent/PL342843A1/xx unknown
- 1999-02-18 JP JP2000532408A patent/JP2002504481A/ja not_active Withdrawn
- 1999-02-18 EE EEP200000468A patent/EE200000468A/xx unknown
- 1999-02-18 HU HU0101280A patent/HUP0101280A3/hu unknown
- 1999-02-18 SK SK1189-2000A patent/SK11892000A3/sk unknown
- 1999-02-18 CA CA002320354A patent/CA2320354A1/en not_active Abandoned
- 1999-02-18 WO PCT/DK1999/000070 patent/WO1999042456A2/en not_active Application Discontinuation
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- 1999-02-18 RU RU2000121882/04A patent/RU2214405C2/ru not_active IP Right Cessation
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2000
- 2000-08-04 IS IS5581A patent/IS5581A/is unknown
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Cited By (17)
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| CN1308317C (zh) * | 2004-01-26 | 2007-04-04 | 瑟维尔实验室 | 新的氟化苯并噻二嗪化合物，它们的制备方法和含有它们的药物组合物 |
| CN102361860A (zh) * | 2009-03-20 | 2012-02-22 | 瑟维尔实验室 | 用作ampa和nmda受体调节剂的苯并硫杂二氮杂*衍生物 |
| CN102361860B (zh) * | 2009-03-20 | 2014-09-10 | 瑟维尔实验室 | 用作ampa和nmda受体调节剂的苯并硫杂二氮杂*衍生物 |
| CN102958919A (zh) * | 2010-07-02 | 2013-03-06 | 霍夫曼-拉罗奇有限公司 | 新的四氢喹啉衍生物 |
| CN103153973A (zh) * | 2010-09-16 | 2013-06-12 | 瑟维尔实验室 | 二氢苯并氧硫氮杂*衍生物、其制备方法、包含此类化合物的药用组合物以及它们作为ampa受体调节剂的用途 |
| CN102977054A (zh) * | 2012-12-12 | 2013-03-20 | 中国药科大学 | 一类选择性α2A受体激动剂的治疗阿尔茨海默病用途 |
| CN103319381A (zh) * | 2013-06-14 | 2013-09-25 | 湖州康企药业有限公司 | 一种高纯度精磺胺的制备方法 |
| CN103319381B (zh) * | 2013-06-14 | 2014-08-27 | 湖州康企药业有限公司 | 一种高纯度精磺胺的制备方法 |
| CN105294599A (zh) * | 2015-09-17 | 2016-02-03 | 三峡大学 | 一种噻二嗪类化合物及其不对称的合成方法 |
| CN106946920A (zh) * | 2017-04-05 | 2017-07-14 | 泰力特医药（湖北）有限公司 | 一种4‑氨基苯硼酸衍生物的制备方法 |
| WO2020253860A1 (zh) * | 2019-06-21 | 2020-12-24 | 江苏豪森药业集团有限公司 | 芳基磷氧化物类衍生物抑制剂、其制备方法和应用 |
| CN112469713A (zh) * | 2019-06-21 | 2021-03-09 | 江苏豪森药业集团有限公司 | 芳基磷氧化物类衍生物抑制剂、其制备方法和应用 |
| CN112469713B (zh) * | 2019-06-21 | 2023-09-01 | 江苏豪森药业集团有限公司 | 芳基磷氧化物类衍生物抑制剂、其制备方法和应用 |
| CN111100042A (zh) * | 2019-11-18 | 2020-05-05 | 苏州诚和医药化学有限公司 | 一种2-甲氧基-5-磺酰胺基苯甲酸的制备方法 |
| CN111100042B (zh) * | 2019-11-18 | 2022-05-31 | 苏州诚和医药化学有限公司 | 一种2-甲氧基-5-磺酰胺基苯甲酸的制备方法 |
| CN111018750A (zh) * | 2019-12-19 | 2020-04-17 | 苏州诚和医药化学有限公司 | 一种2,3-二甲氧基-5-磺酰胺基苯甲酸的制备新方法 |
| CN111018750B (zh) * | 2019-12-19 | 2022-05-27 | 苏州诚和医药化学有限公司 | 一种2,3-二甲氧基-5-磺酰胺基苯甲酸的制备新方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| NO20004121D0 (no) | 2000-08-17 |
| SK11892000A3 (sk) | 2001-02-12 |
| RU2214405C2 (ru) | 2003-10-20 |
| WO1999042456A2 (en) | 1999-08-26 |
| AU2512399A (en) | 1999-09-06 |
| ZA991301B (en) | 1999-09-13 |
| PL342843A1 (en) | 2001-07-16 |
| EE200000468A (et) | 2002-04-15 |
| HUP0101280A2 (hu) | 2001-10-28 |
| NO20004121L (no) | 2000-10-17 |
| IS5581A (is) | 2000-08-04 |
| JP2002504481A (ja) | 2002-02-12 |
| CA2320354A1 (en) | 1999-08-26 |
| TR200002427T2 (tr) | 2001-01-22 |
| IL137720A0 (en) | 2001-10-31 |
| NZ506251A (en) | 2003-01-31 |
| WO1999042456A3 (en) | 1999-10-07 |
| AU751384B2 (en) | 2002-08-15 |
| HUP0101280A3 (en) | 2003-02-28 |
| EP1071426A2 (en) | 2001-01-31 |
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